Recent engineering advances in the instrumentation for medical imaging have produced miniaturized versions of x-ray, radionuclear and magnetic resonance scanners for studies in small laboratory animals. This, coupled with increasingly sophisticated, transgenic mouse models, is driving a revolution in the investigation of disease and developmental processes in vivo at the whole-animal level. This interdisciplinary proposal requests funding for a small-animal x-ray computed tomography scanner ("microCT"). The users are in the fields of radiology/nuclear medicine, medicine, pathology, biochemistry/molecular biology, orthopedic surgery, thoracic surgery, oncology and dentistry. The projects relate to bone development and osteoporosis, as well as to chemo- and antiangiognesis therapy of cancer. Applications of the proposed microCT scanner will include anatomic imaging for correlation with functional images from in vivo, small-animal PET and optical imagers; serial monitoring of metastatic tumor development in animal models; serial, in vivo, quantitative monitoring of normal and pathologic bone development and the effects of diet and genetic alteration on bone growth in transgenic murine models; and ultra-high resolution, in vitro, quantitative imaging of bone specimens in relation to bone development and response to diet and genetic modifications. During the last several years, a Molecular Imaging Center has been established at USC with support from an NIH/ NCIP20 planning grant. The requested microCT scanner will be housed and operated in Center's Molecular Imaging Laboratory, where it will complement small-animal PET and optical imaging systems purchased with previous grants from the NCRR. The particular microCT unit requested is well suited for both the in vitro and in vivo applications presented by the users, viz., it provides ultra-high (10 fm) spatial resolution and sophisticated analysis software for bone studies, acceptable radiation dosage for serial scanning applications in living animals, physiologic gating capability for high resolution in vivo scanning and large bore to accommodate the range of animal species used for micro PET studies. Addition of the requested instrument will greatly enhance the information provided by the existing small-animal molecular imaging facility as well as increase the productivity of assembled PHs-funded investigators at USC and Loma Linda University who are working in the areas of cancer and bone development/disease.